G-Quadruplex-Specific Cell-Permeable Guanosine-Anthracene Conjugate Inhibits Telomere Elongation and Induces Apoptosis by Repressing the c-MYC Gene.

We herein report a cell-membrane-permeable molecular probe ADG, prepared by conjugating guanosine with anthracene, selectively interacts with c-MYC G-quadruplex over other promoter and telomeric quadruplexes as well as duplex DNA. NMR spectroscopy suggests that ADG interacts with terminal G-quartets as well as with the nearby G-rich tract (G13-G14-G15 and G8-G9-G10) of c-MYC quadruplex. In vitro cellular studies indicate that ADG represses c-MYC expression by stabilizing its promoter G-quadruplex and alters c-MYC-related cellular events. ADG suppresses hTERT and BCL2 gene expressions in a promoter-independent manner, inhibits elongation of telomere length, and activates apoptotic cascades in cancer cells.

Self-Assembly of a Guanosine Derivative To Form Nanostructures and Transmembrane Channels.

We herein report the self-assembly of a lipophilic bromoguanosine derivative (G1) in homogeneous solution, in the solid state and in planar bilayer membranes. The self-assembly of G1, driven by H-bonding and π-π stacking interactions can form different nano-structures depending on incubation time. The G1 nanostructure is able to bind a bioactive dye like Rose Bengal. In crystal state, it shows ribbon type H-bonding pattern and exhibits birefringence in polarized light. And further, the self-assembled nanostructure of G1 can form discrete transmembrane ion channels in lipid bilayer membranes, enabling passage of potassium ions.

Interferometric focal length measurement of positive and negative lenses using a lateral-shearing cyclic path optical configuration setup and polarization phase-shifting interferometry.

We present a simple interferometric focal length measurement technique for measuring the focal length of positive and negative lenses using a lateral-shearing cyclic path optical configuration (CPOC) setup and polarization phase-shifting interferometry (PPSI). The technique requires an auxiliary lens, whose focal length need not be known accurately, for generating a focused point source at its focal plane. The focal point of the test lens is adjusted to be in the vicinity of the focus of the auxiliary lens. The radii of the resulting spherical wave fronts emerging from the test lens, due to the defocus, for two different longitudinal shifted positions of the test lens are measured using the lateral-shearing CPOC setup and PPSI. Focal length of the test lens is determined from the known longitudinal shift and from the measured radii of the spherical wave fronts. Results obtained for 200.0 mm convex and 100.0 mm concave test lenses are presented.

Measurement of the surface form error of large aperture plane optical surfaces with a polarization phase-shifting liquid reference reflection Fizeau interferometer.

A polarization phase-shifting liquid reference reflection Fizeau interferometer has been proposed. A polarization cyclic path optical configuration along with a concave telescope mirror is used to produce a pair of expanded, collimated p and s polarized beams with a small angular separation between them. The collimated beams are deflected along a vertical direction toward a Fizeau interferometer cavity formed between a liquid surface that acts as a reference surface and a plane test surface. Either the p or s polarized beam is allowed to strike the liquid surface normally and the orientation of the test surface is adjusted to reflect the other beam, having orthogonal linear polarization, in the direction of the normally reflected reference beam from the liquid surface. A combination of a quarter-wave plate and linear polarizer is used to apply polarization phase shift between the test and reference beams, and quantitative surface form error is measured by applying phase-shifting interferometry. A method for elimination of the residual system aberration is discussed. Results obtained for an optically polished BK-7 disk of clear aperture diameter ≈160 mm are presented.

A DNA-inspired synthetic ion channel based on G-C base pairing.

A dinucleoside containing guanosine and cytidine at the end groups has been prepared using a modular one-pot azide-alkyne cycloaddition. Single channel analysis showed that this dinucleoside predominantly forms large channels with 2.9 nS conductance for the transport of potassium ions across a phospholipid bilayer. Transmission electron microscopy, atomic force microscopy, and circular dichroism spectroscopy studies reveal that this dinucleoside can spontaneously associate through Watson-Crick canonical H-bonding and π-π stacking to form stable supramolecular nanostructures. Most importantly, the ion channel activity of this G-C dinucleoside can be inhibited using the nucleobase cytosine.

Measurement of displacement and distance with a polarization phase shifting folded Twyman Green interferometer.

A Sagnac interferometer (SI), consisting of a polarization beam splitter (PBS), along with two equally spaced plane mirrors that are inclined at 45° to each other, is transformed into a folded Twyman Green interferometer (TGI) by placing a mirrored parallel plate (MPP) into the hypotenuse arm of the SI. The converging input beam produced by a telescope objective (TO) is split into reflected (s-polarized) and transmitted (p-polarized) components by the PBS. The p- and s-polarized focal spots are made to fall on the mirrored end surfaces of the parallel plate (PP). The retroreflected p- and s-polarized beams become collimated after passing through the TO. A linear shift of the PP in either (longitudinal) direction alters the positions of the p- and s-polarized focal spots and results in a set of converging and diverging spherical wavefronts that interfere to form concentric circular fringes. We applied polarization phase-shifting interferometry to obtain the optical path difference (OPD) variation of the interference field. The displacement is calculated from the OPD variation. A validation experiment has been carried out by introducing known shifts to the PP. The setup can be used for displacement as well as distance measurement.

Triazole-tailored guanosine dinucleosides as biomimetic ion channels to modulate transmembrane potential.

A "click" ion channel platform has been established by employing a clickable guanosine azide or alkyne with covalent spacers. The resulting guanosine derivatives modulated the traffic of ions across the phospholipid bilayer, exhibiting a variation in conductance spanning three orders of magnitude (pS to nS). Förster resonance energy transfer studies of the dansyl fluorophore with the membrane binding fluorophore Nile red revealed that the dansyl fluorophore is deeply embedded in the phospholipid bilayer. Complementary cytosine can inhibit the conductance of the supramolecular guanosine channels in the phospholipid bilayers.

Determination of the surface form error of a spherical mirror with phase shifting Sagnac interferometer.

A polarization Sagnac interferometer (SI) is used to produce two laterally separated, identical, convergent emergent beams with linear orthogonal polarizations. The emergent p-polarized and s-polarized beams converge toward their respective focal points. The test and reference spherical mirrors are placed at confocal positions with respect to the s and p focal points so as to normally reflect back the test and reference beams through the SI that recombines the test and reference waves. Polarization phase shifting interferometry is applied to obtain the surface form error of the test surface with respect to the reference surface. A two-step measurement procedure eliminates the system aberrations. Results obtained for a concave spherical test surface with respect to a convex spherical reference surface are presented. The optical configuration is relatively less susceptible to external mechanical vibration.

A fluorescent guanosine dinucleoside as a selective switch-on sensor for c-myc G-quadruplex DNA with potent anticancer activities.

Like likes like! A novel fluorescent C2 -symmetric guanosine-based dinucleoside has been engineered by chemical ligation of two guanosine units with a biocompatible dansyl tag. The nucleoside exhibits high selectivity for c-myc G-quadruplex DNA through fluorescence enhancement over duplex DNA and other promoter G-quadruplexes (see scheme). It stains the nucleus preferentially, arrests the cell cycle at the G2/M phase, inhibits cell growth, and induces apoptosis in A375 cancer cells.

Determination of the index inhomogeneity of transparent isotropic optical material with a dual Sagnac interferometer.

A technique for the measurement of inhomogeneity of optical glass, fused silica, etc., using a Sagnac interferometer (SI) has been presented. An SI produces a pair of laterally separated, mutually parallel, collimated beams with orthogonal planes of polarization, i.e., p and s polarizations from an expanded, linearly polarized (45°) collimated He-Ne (632.8 nm) input laser beam. The p and s beams pass through a liquid-filled cell with plane parallel glass windows. The test glass with plane parallel end surfaces is kept in the path of the p beam in the index matching liquid, while the s beam traverses a parallel path through the liquid. Another SI recombines the emergent p and s beams by removing the lateral shear. A quarter-wave plate transforms the state of polarization of the beams to opposite circular polarizations of which the components selected by a linear polarizer interfere to form Fizeau fringes. Polarization phase shifting interferometery has been applied to determine the optical path difference (OPD) variations. The OPD variation without the test glass is subtracted from that with test glass to eliminate the effect of system aberration. The results for a phosphate laser glass sample have been presented.

Diffusion and birefringence of bioactive dyes in a supramolecular guanosine hydrogel.

Transparent self-standing supramolecular hydrogels were readily prepared by the potassium-ion-mediated self-organization of guanosine and 8-bromoguanosine whilst the individual components precipitated within a few hours. VT-NMR spectroscopy showed that bromoguanosine was a superior gelator compared to guanosine. XRD analysis showed that gel formation was caused by stacked G-quartets. AFM analysis revealed dendritic architectures of the nanofibers in the two-component hydrogel network. DSC profiles showed that the hybrid hydrogels underwent sol-gel transition at lower temperature than the pure guanosine and bromoguanosine hydrogels. Interestingly, bioactive dyes, such as rose bengal, rhodamine-6-G, and fluorescein, could be diffused and released in a controlled manner. UV/Vis absorption and fluorescence spectroscopy and CLSM were used to investigate the diffusion behavior of dyes in the hydrogel network. These dyes exhibited strong birefringence in the gel network (0.07-0.1) as a result of the anisotropic organization.

Opaque optics thickness measurement using a cyclic path optical configuration setup and polarization phase shifting interferometry.

Thickness measurement of an opaque optics using a cyclic path optical configuration (CPOC) setup and polarization phase shifting interferometry (PPSI) is presented. The CPOC setup is used to simultaneously focus two orthogonally polarized counterpropagating converging beams at its hypotenuse arm. The opaque optics is placed at the hypotenuse arm of the CPOC setup such that one of its surfaces reflects back one of the counterpropagating focusing beams. Because of the thickness of the opaque optics, the other focusing beam suffers a longitudinal shift in the beam focus. Applying PPSI, the longitudinal shift in the beam focus which is twice the thickness of the opaque optics is determined. The results obtained for a silicon plate of thickness 0.660 mm with a measurement uncertainty of 0.013 mm are presented.

Simultaneous determination of refractive index and thickness of moderately thick plane-parallel transparent glass plates using cyclic path optical configuration setup and a lateral shearing interferometer.

We present a simple technique for simultaneous determination of refractive index and thickness of moderately thick plane-parallel transparent glass plates (GPs) using a cyclic path optical configuration (CPOC) setup and a wedge shear plate as lateral shearing interferometer. The CPOC setup is used to simultaneously focus the counterpropagating converging beams at a common point at its hypotenuse arm. The apparent thickness and real thickness of the test GP are determined by observing three retrocollimation positions of the GP surfaces with respect to the common focus point. The RI is obtained by dividing the real thickness with apparent thickness of the GP. Presented in this paper are the results obtained for a test GP with a thickness of 14.983 mm and a RI of 1.515.

Self-referenced technique for the determination of meridional figure errors of a toroidal mirror with a Sagnac interferometer.

A simple, self-referenced technique for the determination of meridional surface slope errors of toroidal mirrors (TMs) used in synchrotron radiation is presented. An expanded, collimated, linearly polarized laser beam is allowed to fall on a TM, and the reflected toric wavefront from the TM is allowed to enter a Sagnac interferometer based lateral shearing interferometer setup, which duplicates the beam into identical wavefront components having orthogonal linear polarizations, i.e., p and s polarizations, and introduces appropriate lateral shear between the identical pair of wavefronts along the meridional direction. The laterally sheared identical wavefronts interfere when brought to the same state of polarization. The optical path difference (OPD) variation along the direction of the lateral shear in the interference field is a map of the slope variation. Polarization phase shifting interferometery has been applied to find the OPD variation and thus the slope distribution and errors. Results obtained for a TM of moderately long average radius of curvature along the central meridional section and a relatively shorter radius of curvature along the sagittal section are presented and compared with that obtained with a long trace profiler.

Measurement of longitudinal displacement using lateral shearing cyclic path optical configuration setup and phase shifting interferometry.

We present a technique for the measurement of longitudinal displacement using a lateral shearing cyclic path optical configuration (CPOC) setup and phase shifting interferometry. In the technique, a plane mirror mounted on a linear translation stage, placed slightly away from the focal plane of a lens, introduces a longitudinal focal shift to the incident focusing beam. The resulting spherical wavefront emerging from the lens is sheared into two orthogonally polarized beams using the CPOC setup. By applying polarization phase shifting interferometry (PPSI), the longitudinal focal shift of the beam focus is calculated by determining the slope of the optical path difference variation between the sheared beams. Similarly, the additional focal shift introduced due to longitudinal translation of the mirror, by an unknown amount, is determined using PPSI. Half of the difference between the two longitudinal focal shifts measured gives the longitudinal displacement of the mirror. The technique can be used for an extended range of distance measurement. The novelty of the technique is the introduction of CPOC for the distance measurement. The advantages of the technique compared to other related methods are discussed.

Measurement of the surface profile of an axicon lens with a polarization phase-shifting shearing interferometer.

We present a Twyman-Green interferometer (TGI)-based polarization phase-shifting shearing interferometric technique for testing the conical surface of an axicon (AX) lens. In this technique, the annular beam generated due to the passing of an expanded collimated laser beam traveling along the axis of revolution of the transparent glass AX element is split up into its reflected and transmitted components, having the plane of polarization in the orthogonal planes, by the polarization beam splitter (PBS) cube of the TGI-based optical setup. The split-up components are made to travel unequal paths along the two arms of the TGI and are recombined by the PBS. Because of the difference in path lengths traveled by the annular conical beams, a linear shear is introduced along the radial direction between the interfering components. Thus, the resulting interference pattern gives a map of the optical path difference (OPD) between two successive close points along a radial direction on the conical surface of the AX lens. The OPD map along radial directions, and hence the slopes/profiles of the conical surface, are obtained by applying polarization phase-shifting interferometry. Results obtained for an AX lens are presented.

Measurement of the surface profile of a curved optical surface with rotation phase-shifting lateral shear cyclic path optical configuration.

We present a new (to our knowledge) technique for introducing phase shifts between the laterally sheared emergent beam components of a cyclic path optical configuration (CPOC). The phase shifts are introduced by applying a small change in the angle of incidence of the incident beam due to the small angular rotation of the CPOC setup. Phase-shifting interferometry has been applied along with this phase-shifting technique for a CPOC with lateral shear to find the surface slope/profile of curved optical surfaces. Results for a spherical optical surface have been discussed. An optical setup for measurement of the surface profile of toroidal beam line mirrors of synchrotron radiation sources is proposed.

Thickness measurement of transparent glass plates using a lateral shearing cyclic path optical configuration setup and polarization phase shifting interferometry.

We present a measurement technique to determine the thickness of a transparent glass plate (GP) by using a lateral shearing cyclic path optical configuration (CPOC) setup and polarization phase shifting interferometry (PPSI). In the technique, the GP introduces a longitudinal shift in the focus of the beam and, as a result, a spherical wavefront emerges from the lens, which is otherwise set for producing a collimated beam. Using CPOC, two laterally sheared orthogonally polarized beams are generated from the incident spherical wavefront. By applying PPSI, the slope of the optical path difference variation between the laterally sheared interfering beams is evaluated, and the radius of the spherical wavefront and the longitudinal shift of the beam focus are calculated. The thickness of the GP is determined from the standard relation between the longitudinal shift of the focus introduced by the GP and the thickness of the GP. Results obtained for a GP of 9.810mm thickness are presented.

Ionophore constructed from non-covalent assembly of a G-quadruplex and liponucleoside transports K+-ion across biological membranes.

The selective transport of ions across cell membranes, controlled by membrane proteins, is critical for a living organism. DNA-based systems have emerged as promising artificial ion transporters. However, the development of stable and selective artificial ion transporters remains a formidable task. We herein delineate the construction of an artificial ionophore using a telomeric DNA G-quadruplex (h-TELO) and a lipophilic guanosine (MG). MG stabilizes h-TELO by non-covalent interactions and, along with the lipophilic side chain, promotes the insertion of h-TELO within the hydrophobic lipid membrane. Fluorescence assays, electrophysiology measurements and molecular dynamics simulations reveal that MG/h-TELO preferentially transports K+-ions in a stimuli-responsive manner. The preferential K+-ion transport is presumably due to conformational changes of the ionophore in response to different ions. Moreover, the ionophore transports K+-ions across CHO and K-562 cell membranes. This study may serve as a design principle to generate selective DNA-based artificial transporters for therapeutic applications.

Simultaneous measurement of refractive index and wedge angle of optical windows using Fizeau interferometry and a cyclic path optical configuration.

We present a new technique for the simultaneous measurement of refractive index and wedge angle of optical windows using Fizeau interferometry and a cyclic path optical configuration (CPOC). Two laterally separated beams are obtained from an expanded collimated beam using an aperture containing two rectangular openings. The test wedge plate is placed in one of the two separated beams. Using CPOC, these two beams are made to overlap and interfere, producing interference fringes in the overlapping region. The beams reflected from the front and back surfaces of the test wedge plate interfere and produce Fizeau fringes. The refractive index is related to the spacing of the above two beam fringes. The wedge angle is determined from the evaluated values of the refractive index and Fizeau fringe spacing. The results obtained for a BK-7 optical window are presented.